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Literature summary for 4.2.99.18 extracted from

  • Batebi, H.; Dragelj, J.; Imhof, P.
    Role of AP-endonuclease (Ape1) active site residues in stabilization of the reactant enzyme-DNA complex (2018), Proteins, 86, 439-453 .
    View publication on PubMed
Search for more literature for 4.2.99.18

Protein Variants

Protein Variants Comment Organism
N212A simulations with substitution of Asn212 by Ala show a Mg2+-ion coordination comparable to that of the wild-type Homo sapiens

KM Value [mM]

KM Value [mM] KM Value Maximum [mM] Substrate Comment Organism Structure
additional information
-
 additional information pKa calculations Homo sapiens

Metals/Ions

Metals/Ions Comment Organism Structure
Mg2+ metal-dependent enzyme Homo sapiens

Organism

Organism UniProt Comment Textmining
Homo sapiens P27695
-
-

Synonyms

Synonyms Comment Organism
AP-endonuclease
-
 Homo sapiens
APE1
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 Homo sapiens
apurinic/apyrimidinic endonuclease 1
-
 Homo sapiens

General Information

General Information Comment Organism
additional information molecular dynamics simulations of Ape1 complexed to its substrate DNA performed for models containing 1 or 2 Mg21-ions as cofactor located at different positions show a complex with 1 metal ion bound on the leaving group site of the scissile phosphate to be the most likely reaction-competent conformation. Active-site residue His309 is found to be protonated based on pKa calculations and the higher conformational stability of the Ape1-DNA substrate complex compared to scenarios with neutral His309. Simulations of the D210N mutant further support the prevalence of protonated His309 and strongly suggest Asp210 as the general base for proton acceptance by a nucleophilic water molecule. Enzyme modelling based on the crystal structure of the phosphorothioate substrate complex with Mn2+ as metal cofactor (PDB ID 5DG0). Residue His309 is essential for substrate binding and the phosphate hydrolysis step. In terms of substrate binding, Tyr171 has the possibility to form a hydrogen bond with the non-bridging oxygen atom of the AP-site Homo sapiens
physiological function apurinic/apyrimidinic endonuclease 1 (Ape1) is an important enzyme in the base excision repair mechanism, responsible for the backbone cleavage of abasic DNA through a phosphate hydrolysis reaction Homo sapiens